Long-Term Neuropsychiatric Disorders on Efavirenz-Based Approaches

Fumaz, Carmina R.; Muñoz-Moreno, Jose A.; Molto, Joseph E.; Negredo, Eugènia; Ferrer, Marcela; Sirera, Guillem; Pérez-Álvarez, Núria; Gomez, Guadalupe; Burger, David M.; Clotet, Bonaventura

doi:10.1097/01.qai.0000147523.41993.47

Cited by 148 publications

(120 citation statements)

References 33 publications

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“…The association of efavirenz use with depression or suicide remains controversial [17][18][19][20]. Unfortunately, investigations attempting to address this issue have been either cross-sectional studies or clinical trials with a relatively short follow-up period.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of long-term NNRTI-based ART on the incidence of depression has been largely unknown to date. Although CNS toxicity is a common side effect of efavirenz, and significant rates of depression and suicidal ideation have been described in uncontrolled studies [17], most controlled, systematic evaluations of the impact of efavirenz on depression have found no evidence that efavirenz-based regimens resulted in an excess of depression [18,19,23]. In recent years, three clinical trials have investigated the impact of switching from efavirenz to another antiretroviral agent on CNS symptoms in patients on a stable, fully suppressive, efavirenz-based regimen [35][36][37].…”

Section: Depression In Hiv-infected Patients 217mentioning

confidence: 99%

“…Efavirenz induces depressive-like behaviour and increases stress response in rats [13], and treatment with this drug is often associated with acute central nervous system (CNS) adverse reactions, including insomnia, dizziness and vivid dreams [14,15]. Although these symptoms generally resolve after a few weeks of efavirenz use, a minority of patients may show longer term neuropsychiatric problems [14][15][16].The association of efavirenz use with depression or suicide remains controversial [17][18][19][20]. Unfortunately, investigations attempting to address this issue have been either cross-sectional studies or clinical trials with a relatively short follow-up period.…”

mentioning

confidence: 99%

“…Unfortunately, investigations attempting to address this issue have been either cross-sectional studies or clinical trials with a relatively short follow-up period. While cases of acute depression and suicidal ideations have indeed been reported [21] and some studies have warned of a high prevalence of depression in efavirenz-treated patients [17,22], others have found no association between efavirenz use and depressive disorders [18,19,23]. In the light of this uncertainty, providers may have doubts about the suitability of using efavirenz in individuals with mood disorders, or those considered to be at risk of depression.…”

mentioning

confidence: 99%

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Risk of clinically significant depression in HIV‐infected patients: effect of antiretroviral drugs

et al. 2013

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ObjectivesWe aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy (ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort. MethodsCoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010. ResultsIn total, 5185 patients (13 089 person-years) participated in the study, of whom 3379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval (CI) 9.01-15.15] and 7.06 (95% CI 5.45-9.13) cases per 1000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio (IRR) 0.53; 95% CI 0.28-0.99], while the likelihood of depression increased in patients of age > 50 years (IRR 1.94;. Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving < 2, 2-4 and > 4 years of ART was 0.72 (95% CI 0.36-1.44), 0.10 (95% CI 0.04-0.25) and 0.05 (95% CI 0.01-0.17), respectively, compared with ART-naïve patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately. ConclusionsThe incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens. Mood disorders may negatively affect medication adherence, disease progression and mortality in HIV-infected patients [5][6][7]. Depressive symptoms at the time of initiating combined antiretroviral therapy (ART) have been associated with slower virological suppression [8] and more rapid virological failure in patients initially responding to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens [9]. A number of studies have reported significantly worse outcomes in depressed compared with nondepressed HIV-infected persons, even after adjusting for adherence [9,10].Risk factors for mood disorders in HIV-infected individuals remain largely unknown and there is limited information about the effect that ART might have on their occurrence. A few small observational studies in the early era of combined ART reported a lower prevalence of depression among persons on ART than in those not receiving ART [11], and a possible improvement in depressive symptoms during therapy with protease inhibitors (PIs) was observed [12]. However, there have been no systematic studies assessing the impact of ART on the incidence of depression.ART in persons with mood di...

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Section: Discussionmentioning

confidence: 99%

Section: Depression In Hiv-infected Patients 217mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Risk of clinically significant depression in HIV‐infected patients: effect of antiretroviral drugs

et al. 2013

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“…These conditions are partially fulfilled for efavirenz. There is a certain ground for dose adjustment by using drug levels, although there is no consensus on the association of pharmacokinetics and efavirenz neuropsychological toxicity [6][7][8]. However, some individuals that present significant neuropsychological toxicity may benefit from dose reduction [9,10].…”

mentioning

confidence: 99%

Optimizing efavirenz treatment: CYP2B6 genotyping or therapeutic drug monitoring?

Rotger

Telenti

2008

Eur J Clin Pharmacol

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Maximizing Knowledge Extraction From Patient‐Reported Outcome Data Using Exposure‐Outcome Item Response Modeling Approach: Understanding Efavirenz‐Induced Central Nervous System Toxicity

Bisaso

Mukonzo

et al. 2020

The Journal of Clinical Pharma

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This investigation was undertaken to maximally extract hidden knowledge from an efavirenz-based trial data set using an item response theory-based approach to exposure-outcome analysis. The aim was to understand the influence of efavirenz exposure on the underlying neuropsychiatric impairment in HIV/AIDS patients. Data from 196 individuals with 4136 neuropsychiatric impairment symptom observations at baseline and 2 and 12 weeks of 600mg efavirenz-based therapy was analyzed. The 7 symptoms were categorized as sleep disorders (3), hallucinations (3), and cognitive impairment (1). A longitudinal item response theory model incorporating 3 latent variables based on the symptom categories and a linear disease progression model with a symptomatic drug effect was developed in NONMEM 7.4.1. The model adequately characterized the observed symptoms and revealed the hidden knowledge on the informativeness of symptoms in characterizing the underlying neuropsychiatric impairment. Informativeness, which was affected by underlying impairment severity and efavirenz therapy duration, varied among symptoms. Sleep disorders were the most efavirenz-sensitive symptom category. Vivid dreams and auditory hallucinations were most informative in their respective symptom categories. Mini-Mental State Examination score cutoff levels used to classify the severity of cognitive impairment did not distinctively correspond with neuropsychiatric impairment severity. Efavirenz treatment effect on the severity of neuropsychiatric impairment was not more than 15%. Simulation of individual symptoms at the 400-mg dose only reduced the prevalence of sleep disorder symptoms. Use of the exposure-item response theory modeling approach maximally extracted hidden knowledge about efavirenz-induced neuropsychiatric impairment and appropriately characterized the impact of dose reduction on specific neuropsychiatric impairment symptoms.

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Long-Term Neuropsychiatric Disorders on Efavirenz-Based Approaches

Cited by 148 publications

References 33 publications

Risk of clinically significant depression in HIV‐infected patients: effect of antiretroviral drugs

Risk of clinically significant depression in HIV‐infected patients: effect of antiretroviral drugs

Optimizing efavirenz treatment: CYP2B6 genotyping or therapeutic drug monitoring?

Maximizing Knowledge Extraction From Patient‐Reported Outcome Data Using Exposure‐Outcome Item Response Modeling Approach: Understanding Efavirenz‐Induced Central Nervous System Toxicity

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